Recently, gene therapy has been actively studied, and applied practically to clinical therapy of various cancers and genetic diseases. Gene therapy is an approach to treat a disease by repairing or correcting a defective gene, and comprises transferring a gene encoding an intended enzyme, cytokine, or the like into a cell of a patient, and allowing to produce the intended substance from the gene in the body, thereby treating the disease. Gene therapy is a medication that controls a basis of life, and has a potential to treat various diseases such as AIDS, rheumatoid arthritis, lifestyle-related diseases, in addition to cancers and genetic diseases.
In gene therapy, transfer efficiency of gene into a target cell is an important factor in the increased efficacy of the therapy. Gene therapy for cancers includes therapies by virus such as adenovirus (Cardiovascular Research, 28, 445 (1994); Science, 256, 808 (1992); Gastroenterology, 106, 1076 (1994); TIBTECH, 11, 182 (1993); J. Biol. Chem, 266, 3361 (1991); Nature Medicine, 1, 583 (1995) and the cited references therein) and those by liposome formulations (Biochem Biophys Acta, 1097, 1 (1991); Human Gene Therapy, 3, 399 (1992); Proc. Natl. Acad. Sci. USA, 89, 11277 (1992)). Transfer efficiency of genes is generally higher in therapy using virus vectors than therapy using liposome formulations. However, therapy using virus vectors suffers from a problem that multiple administrations are hardly conducted due to immunological responses to viruses (J. Biol. Chem., 269, 13695(1994), Am. J. Respir. Cell Mol. Biol., 10, 369 (1994)).
On the other hand, since the analysis on the whole human genetic information (human genome) was almost completed, the focus has been shifted to post-genome strategies how to utilize the accumulated human genetic information in the fields of medication and industry. Specifically, examinations on human gene functions, as well as the structures and functions of the proteins encoded by the gene using the analyzed genetic information have been emphasized. Such a post-genome examinations require the expression and the production of proteins, which necessarily involve the transfer of intended genes into cells. Genes to be transferred into host cells by adenovirus vectors and liposome vectors or plasmid DNA vectors are not integrated into the genome of the cells, and are transiently expressed. Such vectors can not accomplish the constitutive expression of the genes, which is important in gene therapy and analysis on gene functions.